Approach to psychosis

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Psychosis is an impaired perception of reality. It may be caused by a psychiatric disorder (primary psychosis) or it may be the result of substance use, an underlying medical condition, or a mood disorder (secondary psychosis). Acute psychosis is a psychiatric emergency. The management of acute psychosis includes ensuring patient and staff safety, reducing patient agitation, ruling out a medical cause for the thought disturbance, and facilitating the appropriate disposition. Patient agitation may need to be managed before an assessment can be completed; nonpharmacological methods should be attempted first, but rapid escalation to pharmacotherapy may be necessary. Diagnostic testing is guided by the patient's history and clinical presentation. The use of broad, nondirected panels of tests is discouraged. Treatment depends on the underlying cause, but most patients require admission and psychiatry consultation.

• Psychosis: an impaired perception of reality evidenced by one or more of the following thought disturbances ^[2][3]
  • Hallucinations
  • Delusions
  • Disorganized thinking (including speech) or behavior
• Primary psychosis: psychosis resulting primarily from a psychiatric disorder, e.g., schizophrenia ^[4]
• Secondary psychosis: psychosis resulting primarily from a general medical condition and/or the effect of a substance ^[5]
• Psychotic disorder: a disease or condition that produces psychosis

Causes of primary psychosis

Schizophrenia spectrum disorders

The DSM-5-TR also considers schizotypal personality disorder to be a schizophrenia spectrum disorder (see the section on “Personality disorders” for details). ^[2]

Mood disorders and anxiety disorders

• Mood disorder with psychotic features
  • Duration of symptoms
    • Major depressive episode for at least 2 weeks
    • Manic episode lasting ≥ 1 week
  • Clinical features
    • Mood symptoms with or without psychotic symptoms
    • Psychotic symptoms appear exclusively during manic or depressive episodes.
  • Social and occupational functioning: Impaired
• Anxiety disorders with psychotic features: e.g., posttraumatic stress disorder ^[8]

Mood-congruent delusions are usually seen in severe depression/mania (e.g., delusion of worthlessness in depression, grandiose delusions in mania), whereas schizoaffective disorder manifests with delusions that are not congruent with the mood.

Personality disorders ^[9]

• Schizotypal personality disorder
  • Odd and eccentric behavior
  • Magical thinking
  • Discomfort in close relationships
  • Short psychotic episodes may occur with less frequency and severity than in schizophrenia.
• Others: Psychotic features can occur in patients with the following personality disorders but are not characteristic.
  • Schizoid personality disorder
    • Disinterest in social relationships
    • Restricted emotional expression and anhedonia
  • Paranoid personality disorder
    • Distrustful of others
    • Superficial relationships

Causes of secondary psychosis ^[5]

Psychotic disorder due to another medical condition

To make this diagnosis, a causal link must be established between psychosis and the underlying condition, and the psychotic symptoms must not occur solely during delirium. The following medical conditions can cause psychosis:

• Multifactorial disorders: : e.g., delirium
• Autoimmune disorders: , e.g., systemic lupus erythematosus, anti-NMDA receptor encephalitis
• Endocrine disorders: , e.g., hyperthyroidism or thyrotoxicosis, hypercortisolism, Wilson disease
• Metabolic disorders: , e.g., porphyria, vitamin B₁₂ deficiency
• Neurological illness: , e.g., dementia, traumatic brain injury, neoplasm (brain tumors), encephalitis, seizure disorders (e.g., temporal lobe epilepsy)

Substance-induced psychotic disorder

To make this diagnosis, psychosis should be identified as a direct consequence of substance use or withdrawal. The following substances can induce psychosis:

• Recreational substances with psychoactive effects
  • Alcohol
  • Hallucinogens (e.g., phencyclidine)
  • Amphetamines
  • Cocaine
  • Cannabis
• Medications with adverse psychoactive effects
  • Analgesics (e.g., opioids)
  • Sedatives or hypnotics
  • Muscle relaxants (e.g., cyclobenzaprine)
  • Antihistamines (e.g., diphenhydramine)
  • Antidepressants (e.g., SSRIs)
  • Cardiovascular medications (e.g., clonidine)
  • Antihypertensive medications (e.g., methyldopa)
  • Anticonvulsants (e.g., levetiracetam)
  • Antiparkinson medications (e.g., dopaminergics)
  • Chemotherapy agents (e.g., bleomycin)
  • Corticosteroids

Treatment typically includes pharmacotherapy for acute psychosis, abstinence from the triggering substance, and treatment of related substance use disorders. ^[10]

Patients with substance-induced psychosis are more likely to develop primary psychosis over their lifetime. ^[10]

Psychosis is evidenced by hallucinations, delusions, disorganized thought (including speech), and/or disorganized behavior.

Hallucinations

• Definition
  • Hallucinations: perceptual abnormalities in which sensory experiences occur in the absence of external stimuli
  • Illusions: a perceptual abnormality in which real external stimuli are misinterpreted
• Types
  • Auditory (most common)
  • Visual
  • Somatic (tactile)
  • Gustatory
  • Olfactory

Delusions

• Definition: fixed, false beliefs that are maintained despite being contradicted by reality or rational arguments and that are not related to one's religious beliefs or culture
• Types
  • Bizarre delusions: delusions that cannot be true or are inconsistent with the patient's social and cultural norms (e.g., a patient insisting that they can fly)
  • Nonbizarre delusions: delusions that can be true or are consistent with the patient's social and cultural norms (e.g., a patient insisting that they have won the lottery when this is not the case)
• Subtypes
  • Grandiosity: The patient insists that they have special powers or importance.
  • Persecutory: The patient insists that they are being cheated, conspired against, harassed, or harmed in any way. Paranoia is a term often used informally to describe the feelings associated with these delusions, such as the belief of being followed or targeted.
  • Erotomania: The patient believes that other individuals are in love with them.
  • Jealousy: The patient believes their partner is unfaithful without justification.
  • Somatic delusion: The patient believes they are experiencing a bodily function or sensation when there is none present.
  • Mixed delusions: two or more delusions occurring simultaneously; no delusion is predominant over the other
  • Unspecified delusions: a delusion that does not fit the criteria of other types or that cannot be clearly defined, such as ideas of reference, where the patient believes that normal events are of special importance to them (e.g., an individual might feel that a television reporter is talking about them)

Disorganized thought and disorganized speech processes

Disorganized thought refers to a disturbance in the logical connection between thoughts or the flow of thoughts. Disorganized speech is a collection of speech abnormalities that lead to incoherent speech.

• Loose associations: incoherent thinking expressed as illogical, sudden, and frequent changes of topic
• Word salad: incoherent thinking expressed as a sequence of words without a logical connection
• Tangential speech: nonlinear thought expressed as a gradual deviation from a focused idea or question
• Neologisms: the creation of new words with idiosyncratic meanings
• Echolalia: involuntary repetition of another's words or sentences
• Flight of ideas: quick succession of thoughts usually demonstrated in a continuous flow of rapid speech and abrupt changes in topic
• Clang association: use of words based on rhyme patterns rather than meaning
• Circumstantial speech: nonlinear thought expressed as a long-winded manner of explanation, with multiple deviations from the central topic, before finally expressing the central idea
• Thought-blocking: an objective observation of an abrupt ending in a thought process, expressed as a sudden interruption in speech
• Pressured speech: accelerated thoughts that are expressed as rapid, loud, and voluminous speech, often in the absence of social stimulation

Associated clinical features

These features depend on the underlying etiology and may appear as a prodrome, concurrently with psychosis, or after psychosis has resolved.

• Primary psychotic disorders: e.g., negative symptoms of schizophrenia, catatonia, cognitive impairment
• Other psychiatric conditions: E.g., see “Mood disorders,” “Anxiety disorders,” and “Substance use disorders.”
• Underlying medical conditions: e.g., focal neurological deficits

Schizophrenia typically manifests with a prodrome of negative symptoms and psychosis (e.g., social withdrawal) that precedes the positive psychotic symptoms (e.g., hallucinations and bizarre delusions).

A medical assessment is performed in all patients with acute psychosis to differentiate between primary and secondary psychosis and to identify comorbidities that may require medical treatment. ^[11][12]

Initial management ^[4]

• Stabilization: Manage acute agitation if present (see “Approach to the agitated or violent patient” for details).
  • Begin with deescalation techniques.
  • Consider prescribing calming medications.
  • Identify and treat critical causes of agitation.
• Clinical evaluation
  • Include the following as part of a thorough medical history from the patient (or collateral history from friends/family members/care providers) :
    • Previous diagnosis of psychosis
    • Prodromal symptoms (e.g., depression, thought disturbance)
    • Time course of symptom onset (e.g., abrupt onset)
    • History of head trauma or new neurological symptoms (e.g., headache)
    • Medication and drug history
    • Other medical history (e.g., thyroid disease, autoimmune disease, porphyria, Cushing syndrome)
    • Recent life stressors
    • Family history of neurological or psychiatric disorders
  • Include the following in the physical examination: ^[11][12][13]
    • Full set of vital signs
    • Level of consciousness
    • Mental status examination
    • Neurological examination
    • Skin examination
• Diagnostics ^[14]
  • Differentiate primary vs. secondary psychosis through clinical evaluation.
  • Perform workup of secondary psychosis as guided by history and physical examination.
• Treatment
  • Treat any underlying medical conditions, substance intoxication, or withdrawal.
  • Consult psychiatry for further management of primary psychosis. ^[15]

If there is a language or cultural barrier, use a trained interpreter with an awareness of the patient's cultural beliefs. ^[4]

The medical evaluation should indicate whether the patient is medically stable, include recommendations for further medical care if needed, and address whether treatment in a psychiatric facility is medically appropriate. Use of the term “medical clearance” is discouraged. ^[16][17]

Disposition ^[18]

• Hospitalize any patient with psychosis who is a danger to themselves or others: See “Decision-making capacity and legal competence” and “Involuntary commitment.”
• Consult psychiatry for all patients being considered for outpatient treatment.
• Treatment in an outpatient psychiatric facility may be appropriate if:
  • The patient is not a danger to themselves or others.
  • The patient is able to attend the outpatient facility regularly.
  • A receiving facility has been identified and agrees to accept the patient.

Indications for diagnostic testing ^[12]

• First episode of psychosis
• Suspected secondary psychosis ^[11][12]
• Admission to a psychiatric facility that cannot perform diagnostic testing
• Testing as a courtesy for a receiving psychiatric facility with limited resources may be performed but should not delay the patient transfer. ^[11]

Agitated patients may require treatment with an antipsychotic or benzodiazepine to facilitate a diagnostic workup.

A thorough history, physical examination (including vital signs), and cognitive assessment are required for the medical evaluation of patients with psychosis. Further diagnostic studies are not routinely required but may be warranted if secondary psychosis is suspected. ^[11][16]

Differentiating primary from secondary psychosis

Primary psychosis due to schizophrenia is often accompanied by negative symptoms (e.g., diminished emotional expression) and/or abnormal motor behavior (e.g., catatonia). ^[3]

Diagnostic studies for secondary psychosis ^[4][19][20]

• Laboratory studies
  • Initial tests: CBC, BMP, liver chemistries, thyroid function tests
  • Consider:
    • ESR and ANA
    • Vitamin B₁₂
    • Thiamine
    • HIV and syphilis testing
    • Pregnancy test
    • Urine toxicology screen ^[11]
• Imaging ^[19]
  • Modality: MRI head (preferred) or CT head
  • Indications
    • Focal neurological signs or symptoms
    • New seizure activity
    • Altered level of consciousness
    • Symptoms of intracranial pathology
    • Evidence of head trauma
    • Symptoms suggestive of autoimmune encephalitis ^[19]
• Other studies
  • EEG: Consider in patients with abnormal neurological examination findings or a history of seizures.
  • For a comprehensive evaluation of new neurocognitive symptoms, see “Symptom-based diagnostic workup for delirium.”

Management of agitation

For more detailed information, see “Management of the agitated or violent patient.”

• Urgently identify and treat critical causes of agitation.
• Attempt nonpharmacological deescalation techniques if appropriate.
• Ensure patient and staff safety; identify signs of potential for violence.
• Prescribe calming medications if indicated (e.g., the patient's behavior poses a danger to themself and/or others). ^[15]
• Consider physical restraints if violent behavior is refractory to deescalation techniques and calming medications.
• Continue assessment and treatment of the psychosis once agitation has resolved.

Only use physical restraints if all alternatives for managing agitation have failed!

Monitoring for adverse reactions to antipsychotics

• Extrapyramidal symptoms
  • Extrapyramidal symptoms, particularly acute dystonia, may accompany the acute administration of antipsychotics. ^[15]
  • Second-generation antipsychotics have a lower risk for extrapyramidal symptoms than first-generation antipsychotics. ^[23]
  • To reduce the incidence of extrapyramidal symptoms, consider coadministration of an anticholinergic (e.g., benztropine) or an antihistamine (e.g., diphenhydramine) with the antipsychotic medication. ^[15]
  • See “Extrapyramidal symptoms” for more information on treatment, including dosages.
• Cardiac arrhythmias ^[24][25][26]
  • Antipsychotics have the potential to increase the QT interval.
  • Patients with long QT syndrome, particularly those with a QTc interval > 500 ms, are at risk for dysrhythmias, e.g., torsades de pointes. ^[25][26][27]
  • If a patient has an increased baseline QTc interval , choose an antipsychotic with a lower risk of QT prolongation. ^[26]
  • Repeat an ECG after the drug level reaches a steady state; if the QTc interval is now > 450 ms in men or > 460 ms in women, or has increased by > 60 ms, consider an alternative pharmacological agent. ^[26][28]
• Neuroleptic malignant syndrome: a rare but life-threatening complication of antipsychotics ^[29]

Use antipsychotics with caution in patients with prolonged QT intervals.

Definitive treatment

• Primary psychosis
  • Refer to psychiatry for:
    • Initiation of psychological and long-term pharmacotherapy of the psychiatric disorder
    • Differentiation between schizophrenia spectrum disorders with mood symptoms and primary mood disorders with psychotic features
  • See also “Schizophrenia," “Major depressive disorder,” “Bipolar disorder,” and “Anxiety disorders.”
• Secondary psychosis
  • Treatment depends on the underlying cause (see “Causes of secondary psychosis”).
  • Patients frequently require inpatient management until their mental status returns to baseline.
  • See also “Delirium” and “Substance use disorders.”

• Rule out life-threatening causes of an acutely altered mental state (see “Critical causes of AMS”).
• Treat agitation as required to ensure patient and staff safety and facilitate patient assessment.
• Obtain a full history and physical examination.
• If secondary psychosis is suspected, perform diagnostic studies.
• Refer to psychiatry if primary psychosis is suspected.
• Treat underlying conditions if secondary psychosis is suspected.